COPD: systemic glucocorticoids had no clear effect on treatment failure.

Clinical bottom line (level 1b-)

  1. Patients hospitalised with exacerbation of chronic obstructive pulmonary disease who were given systemic glucocorticoids, had no clear difference in treatment failure at 30 days or six months than those given placebo.
  2. Patients given systemic glucocorticoids were more likely to have complications (NNH = 4 at 6 months) .
  3. Patients given glucocorticoids had a shorter initial hospitalisation, and there was a trend to improved short-term outcomes.
Niewoehner et al: New England Journal of Medicine 1999; 340 (25): 1941-1947
Expires May 2003

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: 25 Veterans Affairs medical centre, USA

271 patients (aged mean 68 years, 99% male) exacerbation of chronic obstructive pulmonary disease

Excluded if
  • <50 years old
  • history of less than 30 pack-years of cigarette smoking
  • FEV 1 >1.50
  • asthma
  • use of systemic glucocorticoids within the preceding 30 days
  • coexisting medical conditions that made survival for at least one year unlikely
  • inability to give consent


    • Control Group: (n = 111, 111 analysed): placebo
    Experimental Group: (n = 160, 160 analysed): glucocorticoids for eight weeks ( methylprednisolone iv, 125 mg every 6 hours for 72 hours, followed by once-daily oral prednisone- 40 mg on days 4 to 7, 40 mg on 8-11, 20 mg on days 12-43, 10 mg on 44-50, 5 mg on days 51-57), or for two weeks as above, but oral prednisone 20 mg on days 12 to 15.
    All patients received a broad-spectrum antibiotic for seven days, and used an inhaled beta-adrenergic agonist for the whole six month period.
    97% followed for 6 months
    Outcome notes:
    • treatment failure : death or the need for intubation and mechanical ventilation, readmission because of COPD, or intensification of pharmacologic intervention (use of open label systemic glucocorticoids, high-doe inhaled glucocorticoids, theophylline or combination of them)
    • complications : hyperglycaemia, gastrointestinal bleeding, secondary infection, hypertension, psychiatric disorder, or other adverse effects

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    treatment failure 30 days 37
    (33.3%)    		 37
    (23.1%)    		 31%
    (-2% to 53%)    		 10.2%
    (-0.73% to 21.1%)    		 10
    (NNT = 137 to infinity;
    NNH = 5 to infinity)
    treatment failure 6 months 60
    (54.1%)    		 81
    (50.6%)    		 6%
    (-18% to 26%)    		 3.43%
    (-8.65% to 15.5%)    		 29
    (NNT = 12 to infinity;
    NNH = 6 to infinity)
    complications 6 months 51
    (46.0%)    		 113
    (70.6%)    		 -54%
    (-93% to -23%)    		 -24.7%
    (-36.3% to -13.0%)    		 -4
    (-8 to -3)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    length of initial hospitalisation (days) 9.7
    ()     		8.5
    ()     		1.2
    ( to )

  • After the initial hospitalisation, patients in each group spent about the same time in hospital for COPD (placebo 2.0 days vs 1.9 days); however, patients in the glucocorticoid group spent more time in hospital for reasons other than COPD than those in the placebo group (4.4 vs 1.2 days).
  • FEV1 improved significantly faster in patients given than glucocorticoids than those who did not.
  • There was no clear difference between the two week and eight week glucocorticoid treatment groups. Their results have been combined in the analyses above.

    • Comments

    1. The data for the eight and two week glucocorticoid groups were combined.
    2. When open-label intensification occurred, most patients received corticosteroids, thus, the study design changed from a study of placebo vs. drug, to a delayed drug vs immediate drug design.

    Citation

    1. Niewoehner DE, Erbland ML, Deupree RH, et al: Effect of systemic glucocorticoids on exacerbations of chronic obstructive pulmonary disease. New England Journal of Medicine 1999; 340 (25): 1941-1947
    Contributor: Clare Wotton and Bob Phillips, May 2000
    Reviewer: William Stringer

    Clinical Question.
    Patient COPD
    Intervention or Exposure systemic glucocorticoids
    Comparison placebo
    Outcome exacerbation